Numerous guidelines targeting safe use of opioids for chronic pain have been published but substantial challenges persist in clinical application of best practice recommendations. This article describes a pragmatic approach to clinical care of adults with chronic pain receiving long-term opioid therapy. Three components of care are emphasized: (1) medical and mental health assessment before initiating opioid therapy, (2) clinical surveillance during the course of long-term opioid therapy, and (3) clinical considerations and strategies governing opioid tapering. A pressing need exists for ongoing research to further clarify the optimal role that long-term opioid therapy has in treatment of chronic pain.